Wogonin hosted @ β-cyclodextrin: Structural, electronic and nuclear studies

- Two modes of inclusion of the flavonoid Wogonin in β-CD.
- Several combinations of ONIOM2 method including DFT and DFT-D level of theory.
- Standard statistical thermodynamical parameters were calculated in vacuum and water.
- Intermolecular interactions between Wogonin and β-CD.
- 1H chemical shifts of free and complexed Wogonin.

We investigated the inclusion of Wogonin in β-cyclodextrin using several quantum mechanical models. Among the two considered modes of complexation, both PM3 and ONIOM2 results proved that the lowest energy structure is obtained from 'A' orientation. The most stable geometry presents a partial inclusion of Wogonin with the aromatic ring totally embedded in β-cyclodextrin hydrophobic cavity, while the di-hydroxy methoxy phenyl moiety is protruded out of the secondary rim. The statistical thermodynamic calculations at 1 atm and 298.15 K demonstrated that both in vacuum and in water, the complexation process is exothermic and enthalpically driven. However the nonspontaneous inclusion process in vacuum became spontaneous after explicit solvation of Wogonin:β-cyclodextrin complex in water. Furthermore, the quantification of the donor-acceptor interaction between host and guest molecules is performed via Natural Bond Orbital (NBO) analysis and we deduced that the main driving force stabilizing the inclusion complex are van der Waals interactions with a very weak contribution of hydrogen bonding, better estimated by the M05-2X and WB97X-D methods. Finally, 1H Nuclear Magnetic Resonance (NMR) chemical shifts of free and complexed Wogonin were calculated by the Gauge-Including Atomic Orbital (GIAO) method and compared with available experimental data.